Climate is the most important ecological factor determining the growth, development, and productivity of domestic animals (Adams et al., 1998). Climate changes impact the economic viability of livestock production systems worldwide (Klinedinst et al., 1993) through a variety of routes. These include changes in food availability and quality, changes in pest and pathogen populations, alteration in immunity and both direct and indirect impacts on animal performance, such as growth, reproduction, and lactation. Lack of prior conditioning (acclimatization) to sudden change in weather often results in catastrophic losses in the domestic livestock industry (Thornton et al., 2009) Despite uncertainties in climate variability, the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report identified the “likely range” of increase in global average surface temperature between 0.3 °C and 4.8 °C by the year 2100 (IPCC, 2014). The risk potential associated with livestock production systems due to global warming can be characterized by levels of vulnerability, as influenced by animal performance and environmental parameters (Hahn, 1995). As production levels (e.g., rate of gain, milk production per day, eggs per day) increase, the sensitivity and tolerance to stress increases and, when coupled with an adverse environment, the animal is at greater risk. Nationally, heat stress results in total economic losses ranging between $1.9 and $2.7 billion per year (St-Pierre et al., 2003). Although projected increases in ambient temperatures will result in additional financial losses, the extra metabolic heat resulting from the projected increase in animal productivity will have far greater impact, which has been estimated at between two and four times as much as global warming (St-Pierre et al., 2003; St.-Pierre, 2013). Our understanding of the mechanisms by which environmental stress reduces productivity of domestic animals has greatly improved over the last century (Collier et al., 2017). However, it has been difficult to genetically alter production animals to improve their tolerance to thermal stressors. For example, decades of research using genetically defined populations demonstrated that using conventional crossbreeding approaches to improve resistance to thermal stress in the dairy industry always resulted in lower milk yields in the F1 generation, the same holds true for live weight gain in meat animals (Branton et al., 1974; Frisch and Vercoe, 1977). Therefore, improving productivity in animals exposed to adverse environmental conditions during the last quarter century focused on modifying the environment and improving nutritional management while applying selection pressure on improving yields rather than improving stress resistance. This approach dramatically increased productivity of domestic animals but also increased their sensitivity (reduced their thermal plasticity) to high temperatures in general because of their greater internal heat load. The purpose of this review is to define processes by which domestic animals respond to changes in their environment. These processes are critical to survival but often negatively impact productivity and profitability of livestock operations. However, understanding how these processes are controlled offer opportunities for improving thermal stress resistance.